Lectin from Abelmoschus esculentus reduces zymosan-induced temporomandibular joint inflammatory hypernociception in rats via heme oxygenase-1 pathway integrity and tnf-α and il-1β suppression

Int Immunopharmacol. 2016 Sep:38:313-23. doi: 10.1016/j.intimp.2016.06.012. Epub 2016 Jun 23.

Abstract

Temporomandibular joint (TMJ) disorders show inflammatory components, heavily impacting on quality of life. Abelmoschus esculentus is largely cultivated in Northeastern Brazil for medicinal purposes, having it shown anti-inflammatory activity. We evaluated A. esculentus lectin (AEL) efficacy in reducing zymosan-induced temporomandibular joint inflammatory hypernociception in rats along with the mechanism of action through which it exerts anti-inflammatory activity. Animals were pre-treated with AEL (0.01, 0.1 or 1mg/kg) before zymosan (Zy) injection in the TMJ to determine anti-inflammatory activity. To analyse the possible effect of the hemeoxygenase-1 (HO-1) and the nitric oxide (NO) pathways on AEL efficacy, animals were pre-treated with ZnPP-IX (3mg/kg), a specific HO-1 inhibitor, or aminoguanidine (30mg/kg), a selective iNOS inhibitor, before AEL administration. Von Frey test evaluated inflammatory hypernociception, synovial fluid collection was performed to determine leukocyte counting and myeloperoxidase (MPO) activity 6h after Zy injection, and Evans Blue extravasation determined vascular permeability. TMJ tissue was collected for histopathological analysis (H&E) and immunohistochemistry (TNF-α, IL-1β, HO-1). In addition, TMJ tissue and trigeminal ganglion collection was performed for TNF-α and IL-1β dosage (ELISA). AEL increased inflammatory nociceptive threshold, reduced leukocyte influx along with MPO activity, leukocyte influx into the synovial membrane, and Evans Blue extravasation. It promoted HO-1 overexpression whilst decreased TNF-α and IL-1β expression in the TMJ tissue. AEL reduced TNF-α and IL-1β levels in TMJ tissue and trigeminal ganglion. AEL effects, however, were not observed in the presence of ZnPP-IX. These findings suggest that AEL efficacy depends on TNF-α/IL-1β inhibition and HO-1 pathway integrity.

Keywords: Abelmoschus esculentus; HO-1 pathway; Hypernociception; Temporomandibular joint.

MeSH terms

  • Abelmoschus / immunology*
  • Animals
  • Anti-Inflammatory Agents / therapeutic use*
  • Capillary Permeability / drug effects
  • Heme Oxygenase-1 / antagonists & inhibitors
  • Heme Oxygenase-1 / metabolism*
  • Inflammation / chemically induced
  • Inflammation / drug therapy*
  • Interleukin-1beta / metabolism
  • Male
  • Nitric Oxide Synthase Type II / metabolism
  • Overnutrition / chemically induced
  • Overnutrition / drug therapy*
  • Plant Lectins / therapeutic use*
  • Protoporphyrins / pharmacology
  • Rats
  • Rats, Wistar
  • Signal Transduction / drug effects
  • Temporomandibular Joint / drug effects*
  • Temporomandibular Joint / pathology
  • Tumor Necrosis Factor-alpha / metabolism
  • Zymosan

Substances

  • Anti-Inflammatory Agents
  • Interleukin-1beta
  • Plant Lectins
  • Protoporphyrins
  • Tumor Necrosis Factor-alpha
  • zinc protoporphyrin
  • Zymosan
  • Nitric Oxide Synthase Type II
  • Heme Oxygenase-1